The cellular basis of the impaired immune responses of human lymphocytes from aged donors will be determined. Purified sub-populations of lymphocytes obtained from aged donors will be admixed to comparable subpopulations of lymphocytes obtained from young donors. The effect of such mixing will be analyzed in terms of mitogen induced plaque-forming cell responses. Auto-immune prone strains of mice (NZB, NZW, AND NZB, NZW, Fl) will be immunized with thymus independent and thymus dependent antigens. The kinetics of the increase of the heterogeneity of antibody affinity following immunization will be studied at the cellular level.